肠易激综合征腹痛的发生机制和治疗

目的探讨肠易激综合征腹痛的发生机制及治疗方法。方法选取2011年5月～2012年5月在本院治疗的103例肠易激综合征腹痛患者为研究对象,全部患者给予综合对症治疗,观察其腹痛时间、腹痛次数、腹痛频率和腹痛程度改变情况。结果治疗后,肠易激综合征腹痛患者的腹痛时间明显缩短,腹痛次数减少,腹痛频率降低,腹痛程度明显减轻。结论造成肠易激综合征腹痛的原因有多种,临床对神经系统和胃肠系统作全方位的检查,根据病因对症治疗,可有效缓解其临床症状。     

Antidepressants in the treatment of irritable bowel syndrome and visceral pain syndromes

Irritable bowel syndrome (IBS) is characterized by abdominal pain associated with disordered defecation, which may include urgency and altered stool frequency. Visceral pain syndromes, including IBS, may be effectively treated by a variety of therapies that modulate the interactions between the central and enteric nervous systems. Clinical observations and preliminary data suggest that antidepressants may be efficacious for the treatment of these syndromes. The tricyclic antidepressants (TCAs) have been utilized most extensively in this area, but there is a need for more rigorous efficacy data. Serotonin, an important neurotransmitter in both the central and enteric nervous systems, modifies both motility and sensation in the gut. Recognition of the importance of serotonin in digestive motility and sensation has sparked interest in the use of agents that modify serotonergic transmission in visceral pain syndromes. Pharmacological therapeutics that modulate the biological amines (serotonin, norepinephrine, dopamine and catecholamines) both peripherally and within the central nervous system may offer more effective therapies for these disorders. The selective serotonin reuptake inhibitors are commonly used in clinical practice, but more rigorous, controlled studies are needed to determine their effects beyond the treatment of psychiatric comorbidity. The newer generation antidepressants may provide additional insight into the pathophysiology of the brain-gut interactions and their relationship to functional bowel disorders, providing new therapeutic interventions.     

结肠镜检查中腹部疼痛的评分对肠易激综合征的辅助诊断

目的探讨在结肠镜检查中肠易激综合征(IBS)患者与非IBS功能性胃肠病(FGID)患者及健康对照腹部疼痛水平的差异,以了解结肠镜检查中腹部疼痛评分对肠易激综合征的辅助诊断作用。方法采用一般状况调查问卷、罗马Ⅲ诊断标准和疼痛视觉模拟评分(VAS),对2012年1月至8月来我院内镜室检查的149例IBS患者、56例非IBS FGID患者及77名健康对照进行结肠镜检查中疼痛感知水平的调查及评价。结果IBS组与非IBS组(包括FGID组及健康对照组)疼痛评分[M(P25^P75)]分别为26(19P75)]分别为26(19³9.25)分和23(1539.25)分和23(15³0)分,2组比较差异有统计学意义(P<0.01);FGID组及健康对照组疼痛评分分别为25(1530)分,2组比较差异有统计学意义(P<0.01);FGID组及健康对照组疼痛评分分别为25(15³1.5)分和22(15.531.5)分和22(15.5²8.5)分,IBS组与2组分别比较,差异均有统计学意义(P<0.01)。结论在结肠镜检查过程中,IBS患者腹部疼痛感知水平高于非IBS FGID患者及健康对照;结肠镜检查中腹部疼痛水平评分可作为有效评价IBS患者内脏敏感性的指标,用以辅助诊断IBS。     

小剂量黛力新联合匹维溴胺治疗腹痛型肠易激综合征

目的比较小剂量抗焦虑抑郁药黛力新联合匹维溴胺与单独应用匹维溴胺对腹痛型肠易激综合征的治疗效果。方法将82例腹痛型肠易激综合征（irritable bowel syndrome,IBS）患者随机分成治疗组43例和对照组39例,治疗组给予黛力新片10mg,b．i．d．,分别于早上8点与中午12点分服,匹维溴胺片50mg,t．i．d．。对照组给予匹维溴胺片50mg,t．i．d．,2组疗程均为8周,治疗期间均停用其他药物。观察比较2组疗效。结果治疗组治疗8周的总有效率88．4％,疗效明显高于对照组64．1％,差异有统计学意义（P〈0．05）。结论小剂量黛力新联合匹维溴胺对腹痛型IBS具有良好的治疗效果。     

Treatment of pain symptoms in irritable bowel syndrome patients

Irritable bowel syndrome represents a common gastrointestinal disorder that significantly impacts patients' lives. It is defined by Rome II criteria and characterized by abdominal pain and bloating associated with changes in bowel habit. Visceral hypersensitivity is currently considered a biological marker for the disease. Current therapeutic treatments include the use of fiber supplements, antidiarrheal agents, laxatives, antispasmodics, tricyclic antidepressants and serotonergic agents. Through a proper understanding of the diagnostic criteria, pathophysiology and treatment options, this disorder can be treated effectively in many patients.     

Costs of health care for irritable bowel syndrome, chronic constipation, functional diarrhoea and functional abdominal pain

AIM: To provide estimates of actual costs to deliver health care to patients with functional bowel disorders, and to assess the cost impact of symptom severity, recency of onset, and satisfaction with treatment. METHODS: We enrolled 558 irritable bowel (IBS), 203 constipation, 243 diarrhoea and 348 abdominal pain patients from primary care and gastroenterology clinics at a health maintenance organization within weeks of a visit. Costs were extracted from administrative claims. Symptom severity, satisfaction with treatment and out-of-pocket expenses were assessed by questionnaires. RESULTS: Average age was 52 years, 27% were males, and 59% participated. Eighty percent were seen in primary care clinics. Mean annual direct health care costs were $5049 for IBS, $6140 for diarrhoea, $7522 for constipation and $7646 for abdominal pain. Annual out-of-pocket expenses averaged $406 for treatment of IBS symptoms, $294 for diarrhoea, $390 for constipation and $304 for abdominal pain. Lower gastrointestinal costs comprised 9% of total costs for IBS, 9% for diarrhoea, 6.5% for constipation and 9% for abdominal pain. In-patient care accounted for 17.5% of total costs (15.2% IBS). CONCLUSION: Costs were affected by disease severity (increased), recent exacerbation of bowel symptoms (increased), and whether the patient was consulting for the first time (decreased).     

Review article: clinical pharmacology models of irritable bowel syndrome

This review describes the basis for development of clinical pharmacology models of irritable bowel syndrome (IBS) and presents a critical analysis of current models. IBS is becoming a more circumscribed diagnosis by improved symptom criteria and this is perceived as helpful progress for the development of suitable models. Concepts about the aetiopathogenesis and pathophysiology of IBS are also evolving. Different models have been established to study specific derangements in motor function, visceral reflexes and conscious perception of gut stimuli. The review also focuses on specific examples of drug evaluation using appropriate and validated models.     

Pioglitazone improves visceral sensation and colonic permeability in a rat model of irritable bowel syndrome

Visceral hypersensitivity and impaired gut barrier with minor inflammation are considered to play an important role in the pathophysiology of irritable bowel syndrome (IBS). Since pioglitazone is known to have anti-inflammatory property, we hypothesized that pioglitazone is beneficial for treating IBS. In this study, the effect was tested in rat IBS models such as lipopolysaccharide or repeated water avoidance stress-induced visceral allodynia and increased colonic permeability. Pioglitazone blocked these visceral changes, and GW9662, a peroxisome proliferator-activated receptor gamma (PPAR-γ) antagonist fully reversed the effect by pioglitazone. These results suggest that PPAR-γ activation by pioglitazone may be useful for IBS treatment.     

Alosetron and irritable bowel syndrome

Alosetron (Lotronex^®, GlaxoSmithKline) is a potent and selective 5-HT₃-receptor antagonist approved by the FDA for the treatment of women with diarrhoea-predominant irritable bowel syndrome (IBS) in whom conventional therapy has failed. Studies involving healthy volunteers and IBS patients have demonstrated a beneficial effect of treatment with alosetron on global IBS symptoms, abdominal pain and discomfort, altered bowel function as well as improvement of quality of life (QOL). Data from animals studies suggest the involvement of 5-HT₃ receptors on intrinsic primary afferent neurons in the mediation of the effect of alosetron on gastrointestinal motility and secretion. While definitive proof of a visceroanalgesic action is not available, an additional central mechanism of action is suggested by findings obtained in animal models, as well as from human brain imaging studies. Alosetron shows a greater effectiveness in women, and the role of genetic factors underlying inter-individual differences in the response to alosetron is currently under investigation. The most frequent adverse event associated with the use of alosetron is constipation and in some rare cases, the development of colonic mucosal ischaemia. In the following review, the most recent reported effects of alosetron on gastrointestinal motility, visceral sensitivity and anxiety, both in terms of preclinical and clinical data will be discussed. The impact of alosetron on QOL in IBS patients and the safety of treatment with alosetron, will also be covered.     

Alosetron and irritable bowel syndrome

Alosetron (Lotronex, GlaxoSmithKline) is a potent and selective 5-HT(3)-receptor antagonist approved by the FDA for the treatment of women with diarrhoea-predominant irritable bowel syndrome (IBS) in whom conventional therapy has failed. Studies involving healthy volunteers and IBS patients have demonstrated a beneficial effect of treatment with alosetron on global IBS symptoms, abdominal pain and discomfort, altered bowel function as well as improvement of quality of life (QOL). Data from animals studies suggest the involvement of 5-HT(3) receptors on intrinsic primary afferent neurons in the mediation of the effect of alosetron on gastrointestinal motility and secretion. While definitive proof of a visceroanalgesic action is not available, an additional central mechanism of action is suggested by findings obtained in animal models, as well as from human brain imaging studies. Alosetron shows a greater effectiveness in women, and the role of genetic factors underlying inter-individual differences in the response to alosetron is currently under investigation. The most frequent adverse event associated with the use of alosetron is constipation and in some rare cases, the development of colonic mucosal ischaemia. In the following review, the most recent reported effects of alosetron on gastrointestinal motility, visceral sensitivity and anxiety, both in terms of preclinical and clinical data will be discussed. The impact of alosetron on QOL in IBS patients and the safety of treatment with alosetron, will also be covered.     

Pathophysiology in irritable bowel syndrome

Irritable bowel syndrome (IBS) is a distressing condition that impairs quality of life, and it deserves to be treated. It also has a large economic impact on healthcare utilization and absenteeism. IBS is a disorder in which three major mechanisms interact: altered gastrointestinal motility, increased sensory function of the intestine and psychosocial factors. The role of prior infection in the development of IBS is the subject of ongoing study. This article focuses on pathophysiological mechanisms, including the potential roles of mucosal changes and neurobiology in the development of IBS. Novel pharmacological agents are being developed to target neural mediators of IBS; they appear promising, and their role in clinical practice will be clarified with regulatory approval and clinical use.     

Review article: visceral hypersensitivity in irritable bowel syndrome: molecular mechanisms and therapeutic agents

Background  Although development of visceral pain is an important defensive mechanism, hypersensitivity results in a significant clinical problem and is likely to be one of the major factors involved in the pathogenesis of abdominal and chest pain in functional bowel disorders (FBDs). Understanding of the molecular mechanisms involved in peripheral sensitization of visceral nociceptors has advanced as a result of the experimental studies, especially in animal models, which have led to knowledge and identification of key mediators and receptors.
Aim  To provide a comprehensive review focused on the peripheral mechanisms believed to be responsible for sensitization and potential molecular targets for a disorder which is common, distressing and has sub-optimal treatment options.
Methods  Literature review using Ovid and Pubmed from 1966.
Results  There is substantial interest in the development of new drugs for treatment of FBDs in the background of advances in understanding the molecular and physiological mechanisms of visceral hypersensitivity. The potential drug targets include TPRV1, ASICs, voltage-gated sodium channels, ATP, PAR-2, cannabinoid, prostaglandin, tachykinin and 5HT₃ receptors.
Conclusion  It is anticipated that with advancing molecular understanding of the basis of visceral hypersensitivity, the next decade will see accelerated development of new molecules for treatment of functional bowel diseases.     

Amitriptyline modifies the visceral hypersensitivity response to acute stress in the irritable bowel syndrome

Background  Acute physical stress causes alteration in gut autonomic function and visceral hypersensitivity in patients with irritable bowel syndrome (IBS). We have developed a model to measure this stress response.
Aim  To assess whether treatment with a drug effective in treating IBS (amitriptyline) alters the response to acute stress in IBS patients.
Methods  Nineteen patients with IBS were given amitriptyline 25–50 mg. Patients underwent physical stress (cold pressor) test at baseline and after 3 months of treatment. Physiological parameters measured were: stress perception; systemic autonomic tone [heart rate (HR) and blood pressure (BP)]; gut specific autonomic innervation [rectal mucosal blood flow (RMBF)] and visceral sensitivity (rectal electrosensitivity).
Results  Fourteen of 19 (74%) patients improved symptomatically after 3 months of amitriptyline. Acute stress induced increased perception of stress and systemic autonomic tone and reduced RMBF in symptomatic responders and nonresponders ( P  > 0.05 for all). All nonresponders but only 3 of 14 responders continued to exhibit stress-induced reduced pain threshold at 3 months (change from baseline −31% vs. +2%, P  < 0.03 respectively).
Conclusion  In this open study, amitriptyline appears to decrease stress-induced electrical hypersensitivity; this effect is independent of autonomic tone. The gut response to acute stress deserves further study as a model to study drug efficacy in IBS.